The development of dynamic cardiac single photon emission computed tomography (SPECT) has the potential to offer a sensitive measure of ischemia and to characterize viable myocardium with a versatility of imaging the full armamentarium with versatility of imaging the full armamentarium of available cardiac radio-pharmaceuticals. Dynamic cardiac SPECT holds forth the potential of acquiring more and perhaps better diagnostic information than static studies at no additional cost aside from computational processing. The hypothesis is that estimates of pharmacokinetics of radiotracers are more sensitive measures of cardiac disease than visual interpretations of static images. The proposed work will develop methods of processing dynamic cardiac SPECT data of 99m/Tc-teboroxime and 201/Tl in canine models and patients. Dynamic cardiac SPECT using single- and multi- detector SPECT systems will be used in development of new algorithms that reconstruct 3D images of the physiological kinetic model parameters of the heart without artifacts from dynamically acquired tomographic projects. The following will be achieved: (1) Development of iterative and direct matrix inverse algorithms for reconstructing dynamic SPECT data. (2) Development of algorithms for estimating kinetic model parameters directly from projection measurements. (3) Development of automatic segmentation of regions of interest and generation of time activity curves for blood, myocardial, and background tissue. (4) An analysis of effects of SPECT physics and human physiology on the bias and variance of estimated kinetic parameters. (5) Development of a sensitive measure of ischemic and viable myocardium using estimated kinetic parameters of 99m/Tc-teboroxime and 201/Tl. The proposed work will develop applied mathematical tools to accurately and precisely quantify kinetic parameters and systematically evaluate these methods with computer simulations, canine experiments, and clinical studies. The goal of this proposal is to develop methods that use existing single- and multi-detector SPECT systems; and, in so doing, make dynamic SPECT useful even in those clinics which have only single- detector SPECT systems and are thus not able to perform rapid acquisitions. The developed techniques will provide improved health care through better detectability of myocardial infarcts, better diagnosis of ischemic heart disease, and better evaluation of tissue viability without additional cost for the SPECT procedure. Many of the methods developed will also be applicable to imaging the myocardium with glucose analogues such as 18FDG and fatty acids such as 123IPPA. It is anticipated that these techniques will be applicable to imaging other organ systems such as the kidney and the brain.